β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors

C Fernández-Lainez; R Akkerman; M.M.P. Oerlemans; M.J. Logtenberg; H.A. Schols; L.A. Silva Lagos; G. López-Velázquez; Paul de Vos

doi:10.1016/j.carbpol.2021.118893

β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors

C Fernández-Lainez
, R Akkerman
, M.M.P. Oerlemans
, M.J. Logtenberg
, H.A. Schols
, L.A. Silva Lagos
, G. López-Velázquez
, Paul de Vos

Rijksuniversiteit Groningen, Universitair Medisch Centrum Groningen, Afdeling Pathologie en Medische Biologie, Sectie Immuno-endocrinologie
Instituto Nacional de Pediatría, Laboratorio de Errores innatos del Metabolismo y Tamiz
Universidad Nacional Autónoma de México (UNAM), Posgrado en Ciencias Biológicas
Wageningen University & Research, Laboratory of Food Chemistry
Instituto Nacional de Pediatría, Laboratorio de Biomoléculas y Salud Infantil

Onderzoeksoutput: Article › Academic › peer review

Samenvatting

Graminan-type fructans (GTFs) have demonstrated immune benefits. However, mechanisms underlying these benefits are unknown. We studied GTFs interaction with Toll-like receptors (TLRs), performed molecular docking and determined their impact on dendritic cells (DCs). Effects of GTFs were compared with those of inulin-type fructans (ITFs). Whereas ITFs only contained β(2→1)-linked fructans, GTFs showed higher complexity as it contains additional β(2→6)-linkages. GTFs activated NF-κB/AP-1 through MyD88 and TRIF pathways. GTFs stimulated TLR3, 7 and 9 while ITFs activated TLR2 and TLR4. GTFs strongly inhibited TLR2 and TLR4, while ITFs did not inhibit any TLR. Molecular docking demonstrated interactions of fructans with TLR2, 3, and 4 in a structure dependent fashion. Moreover, ITFs and GTFs attenuated pro-inflammatory cytokine production of stimulated DCs. These findings demonstrate immunomodulatory effects of GTFs via TLRs and attenuation of cytokine production in dendritic cells by GTFs and long-chain ITF.

Originele taal-2	English
Artikelnummer	118893
Tijdschrift	Carbohydrate Polymers
Volume	277
Vroegere onlinedatum	15 nov. 2021
DOI's	https://doi.org/10.1016/j.carbpol.2021.118893
Status	Published - 8 dec. 2021
Extern gepubliceerd	Ja

Keywords

vertakte fructanen
functionele voeding
immunomodulatie
niet-verteerbare koolhydraten
Toll-achtige receptoren

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10.1016/j.carbpol.2021.118893Licentie: CC BY

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title = "β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors",

abstract = "Graminan-type fructans (GTFs) have demonstrated immune benefits. However, mechanisms underlying these benefits are unknown. We studied GTFs interaction with Toll-like receptors (TLRs), performed molecular docking and determined their impact on dendritic cells (DCs). Effects of GTFs were compared with those of inulin-type fructans (ITFs). Whereas ITFs only contained β(2→1)-linked fructans, GTFs showed higher complexity as it contains additional β(2→6)-linkages. GTFs activated NF-κB/AP-1 through MyD88 and TRIF pathways. GTFs stimulated TLR3, 7 and 9 while ITFs activated TLR2 and TLR4. GTFs strongly inhibited TLR2 and TLR4, while ITFs did not inhibit any TLR. Molecular docking demonstrated interactions of fructans with TLR2, 3, and 4 in a structure dependent fashion. Moreover, ITFs and GTFs attenuated pro-inflammatory cytokine production of stimulated DCs. These findings demonstrate immunomodulatory effects of GTFs via TLRs and attenuation of cytokine production in dendritic cells by GTFs and long-chain ITF.",

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AU - Fernández-Lainez, C

AU - Akkerman, R

AU - Oerlemans, M.M.P.

AU - Logtenberg, M.J.

AU - Schols, H.A.

AU - Silva Lagos, L.A.

AU - López-Velázquez, G.

AU - de Vos, Paul

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N2 - Graminan-type fructans (GTFs) have demonstrated immune benefits. However, mechanisms underlying these benefits are unknown. We studied GTFs interaction with Toll-like receptors (TLRs), performed molecular docking and determined their impact on dendritic cells (DCs). Effects of GTFs were compared with those of inulin-type fructans (ITFs). Whereas ITFs only contained β(2→1)-linked fructans, GTFs showed higher complexity as it contains additional β(2→6)-linkages. GTFs activated NF-κB/AP-1 through MyD88 and TRIF pathways. GTFs stimulated TLR3, 7 and 9 while ITFs activated TLR2 and TLR4. GTFs strongly inhibited TLR2 and TLR4, while ITFs did not inhibit any TLR. Molecular docking demonstrated interactions of fructans with TLR2, 3, and 4 in a structure dependent fashion. Moreover, ITFs and GTFs attenuated pro-inflammatory cytokine production of stimulated DCs. These findings demonstrate immunomodulatory effects of GTFs via TLRs and attenuation of cytokine production in dendritic cells by GTFs and long-chain ITF.

AB - Graminan-type fructans (GTFs) have demonstrated immune benefits. However, mechanisms underlying these benefits are unknown. We studied GTFs interaction with Toll-like receptors (TLRs), performed molecular docking and determined their impact on dendritic cells (DCs). Effects of GTFs were compared with those of inulin-type fructans (ITFs). Whereas ITFs only contained β(2→1)-linked fructans, GTFs showed higher complexity as it contains additional β(2→6)-linkages. GTFs activated NF-κB/AP-1 through MyD88 and TRIF pathways. GTFs stimulated TLR3, 7 and 9 while ITFs activated TLR2 and TLR4. GTFs strongly inhibited TLR2 and TLR4, while ITFs did not inhibit any TLR. Molecular docking demonstrated interactions of fructans with TLR2, 3, and 4 in a structure dependent fashion. Moreover, ITFs and GTFs attenuated pro-inflammatory cytokine production of stimulated DCs. These findings demonstrate immunomodulatory effects of GTFs via TLRs and attenuation of cytokine production in dendritic cells by GTFs and long-chain ITF.

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KW - functionele voeding

KW - immunomodulatie

KW - niet-verteerbare koolhydraten

KW - Toll-achtige receptoren

KW - Branched-chain fructans

KW - Functional food

KW - Immunomodulation

KW - Non-digestible carbohydrates

KW - Toll-like receptors

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M1 - 118893

ER -

β(2→6)-Type fructans attenuate proinflammatory responses in a structure dependent fashion via Toll-like receptors

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Keywords

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